Analysis by Liquid Chromatography - Mass Spectrometry of Sterols and Oxysterols in Brain of the Newborn Dhcr7Δ3-5/T93M Mouse: A Model of Smith-Lemli-Opitz Syndrome

In this study the sterol and oxysterol profile of newborn brain from the Dhcr7Δ3-5/T93M mouse model of Smith-Lemli-Opitz syndrome (SLOS) has been investigated. This is a viable mouse model which is compound heterozygous containing one null allele and one T93M mutation on Dhcr7. We find the SLOS mouse has reduced levels of cholesterol and desmosterol and increased levels of 7- and 8-dehydrocholesterol and of 7- and 8-dehydrodesmosterol in brain compared to the wild type. The profile of enzymatically formed oxysterols in the SLOS mouse resembles that in the wild type but the level of 24S-hydroxycholesterol, the dominating cholesterol metabolite, is reduced in a similar proportion to that of cholesterol. A number of oxysterols abundant in the SLOS mouse are probably derived from 7-dehydrocholesterol, however, the mechanism of their formation is unclear